Syntheses of stable, synthetic diadenosine polyphosphate analogues using recombinant histidine-tagged lysyl tRNA synthetase (LysU)

WrightM.; AzharM.A.; KamalA.; MillerA.D.

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Syntheses of stable, synthetic diadenosine polyphosphate analogues using recombinant histidine-tagged lysyl tRNA synthetase (LysU)

机译：使用重组组氨酸标记的赖氨酰tRNA合成酶（LysU）合成稳定的合成腺苷多磷酸类似物

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Recombinant Escherichia coli lysyl-tRNA synthase (LysU) has been previously utilised in the production of stabile, synthetic diadenosine polyphosphate (ApnA) analogues. Here we report on the extended use of a new recombinant histidine residue-tagged LysU as a tool for highly controlled phosphatephosphate bond formation between nucleotides, avoiding the need for complex protecting group chemistries. Resulting high yielding tandem LysU-based biosynthetic-synthetic/synthetic-biosynthetic strategies emerge for the preparation of varieties of ApnA analogues directly from inexpensive natural nucleotides and nucleosides. Analogues so formed make a useful small library with which to probe ApnA activities in vitro and in vivo leading to the discovery of new, potentially potent biopharmaceuticals active against chronic pain and other chronic, high-burden disease states.

机译：重组大肠杆菌赖氨酰-tRNA合酶（LysU）先前已用于生产稳定的合成二磷酸腺苷多磷酸腺苷（ApnA）类似物。在这里，我们报告了新的重组组氨酸残基标记的LysU的广泛使用，作为在核苷酸之间高度可控的磷酸磷酸酯键形成的工具，从而无需使用复杂的保护基化学物质。由此产生的高产量串联的基于LysU的生物合成/合成/生物合成策略可直接从廉价的天然核苷酸和核苷制备各种ApnA类似物。如此形成的类似物成为有用的小型文库，可用于在体外和体内探查ApnA活性，从而导致发现了对慢性疼痛和其他慢性高负担疾病状态具有活性的新的，可能有效的生物药物。

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《Bioorganic and Medicinal Chemistry Letters》 |2014年第10期|共7页
作者
WrightM.; AzharM.A.; KamalA.; MillerA.D.;
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Analogues; Biosynthesis; Diadenosine polyphosphate; Dinucleoside polyphosphates; Lysyl tRNA synthetase (LysU);

机译：类似物;生物合成;多磷酸腺苷;多磷酸二核苷;赖氨酰tRNA合成酶（LysU）;

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1. Syntheses of stable, synthetic diadenosine polyphosphate analogues using recombinant histidine-tagged lysyl tRNA synthetase (LysU) [J] . WrightM., AzharM.A., KamalA., Bioorganic and Medicinal Chemistry Letters . 2014,第10期

机译：使用重组组氨酸标记的溶羟基合成酶（Lysu）合成稳定的合成二值二磷酸二磷酸二磷酸二磷酸盐类似物（Lysu）
2. Escherichia coli LysU is a potential surrogate for human lysyl tRNA synthetase in interactions with the C-terminal domain of HIV-1 capsid protein [J] . Nonlawat Boonyalai, James R. Pullen, Mohd Firdaus Abdul Wahab, Organic & biomolecular chemistry . 2013,第4期

机译：大肠杆菌LysU在与HIV-1衣壳蛋白C末端结构域相互作用的过程中是人类赖氨酰tRNA合成酶的潜在替代物
3. Multiple catalytic activities of Escherichia coii lysyl-tRNA synthetase (LysU) are dissected by site-directed mutagenesis [J] . Xiaolong Chen, Nonlawat Boonyalai, Catherine Lau, The FEBS journal . 2013,第1期

机译：大肠埃希氏菌赖氨酰-tRNA合成酶（LysU）的多个催化活性通过定点诱变来解剖。
4. Regulation of tRNALys Packaging into HIV-1 by Lysyl tRNA Synthetase [C] . 19th tRNA workshop tRNA 2002"" . 2002

机译：赖氨酰tRNA合成酶对tRNALys包装入HIV-1的调控
5. Lysyl-tRNA Synthetase-Capsid Interaction in Human Immunodeficiency Virus-1: Implications for the Priming of Reverse Transcription and Therapeutic Development. [D] . Dewan, Varun. 2012

机译：人类免疫缺陷病毒-1中的赖氨酰-tRNA合成酶-衣壳相互作用：逆转录和治疗发展的启动的影响。
6. The crystal structures of T. thermophilus lysyl-tRNA synthetase complexed with E. coli tRNA(Lys) and a T. thermophilus tRNA(Lys) transcript: anticodon recognition and conformational changes upon binding of a lysyl-adenylate analogue. [O] . S Cusack, A Yaremchuk, M Tukalo 1996

机译：与大肠杆菌tRNA（Lys）和嗜热衣原体tRNA（Lys）转录物复合的嗜热衣原体赖氨酰-tRNA合成酶的晶体结构：赖氨酸-腺苷酸类似物结合后的反密码子识别和构象变化。
7. The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli [O] . Onesti Silvia, Miller Andrew D, Brick Peter 1995

机译：大肠杆菌的赖氨酰-tRNA合成酶（LysU）的晶体结构
8. Compositions of Orthogonal Lysyl-tRNA and Aminoacyl-tRNA Synthetase Pairs and Uses Thereof (PAT-APPL-11-326 970). [R] . Anderson, J. C., Wu, N., Santoro, S., 2006

机译：正交赖氨酰-tRNa和氨基酰基-tRNa合成酶对的组成及其用途（paT-appL-11-326 970）。

Syntheses of stable, synthetic diadenosine polyphosphate analogues using recombinant histidine-tagged lysyl tRNA synthetase (LysU)

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